ABSTRACT
PURPOSE: Melanoma cells can be found in the circulation of patients with melanoma. The following study was conducted to examine whether changes in their presence could provide an early marker of response to therapy. EXPERIMENTAL DESIGN: We measured the presence of several markers of melanoma cells in the peripheral blood of 118 patients with resected stage IIb, III, or IV melanoma before and after immunotherapy with a polyvalent, shed antigen, melanoma vaccine using reverse transcription-PCR assays for tyrosinase, gp100, MART-1, and MAGE-3. Assays were conducted at baseline and after 3, 5, and 11 months of therapy. RESULTS: Overall, 47% of patients were positive for at least one marker during the study. Before vaccine treatment, circulating melanoma cell markers were present in 23% of patients. After 5 and 7 months of vaccine therapy, the proportion of patients with circulating markers decreased by 27% and 55%, respectively (P for trend = 0.02). The recurrence-free survival of patients whose melanoma cell markers disappeared during vaccine treatment was significantly longer than that of patients in whom they increased, i.e., the percentage of patients who were recurrence free at 1 year was 80% versus 58% (P = 0.03). CONCLUSIONS: Therapy with a polyvalent melanoma vaccine was associated with clearance of melanoma cell markers from the circulation, and the clearance was associated with an improved prognosis. These findings suggest that the sequential assay of tumor cells in the circulation by reverse transcription-PCR may provide an early indication of the effectiveness of cancer therapy.
Subject(s)
Biomarkers, Tumor , Melanoma/blood , Melanoma/therapy , Neoplastic Cells, Circulating/metabolism , Adolescent , Adult , Aged , Disease-Free Survival , Female , Humans , Immunotherapy/methods , Male , Melanoma/metabolism , Melanoma/mortality , Middle Aged , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: Vaccine-induced antitumor CD8+ T-cell responses are believed to play an important role in increasing resistance to melanoma. The following study was conducted to examine whether these responses are associated with improved clinical outcome in melanoma vaccine-treated patients. EXPERIMENTAL DESIGN: We measured CD8+ T-cell responses to gp100, MART-1, MAGE-3, and tyrosinase by enzyme-linked immunospot assay in peripheral blood of 131 HLA-A*01- or HLA-A*02-positive melanoma patients before and after immunization to a polyvalent, shed antigen, melanoma vaccine, and correlated the results with clinical outcome. RESULTS: Fifty-six percent of patients had a vaccine-induced CD8+ T-cell response to at least one of the four antigens. Recurrences were significantly reduced in patients with vaccine-induced responses to MAGE-3 (hazard ratio, 0.42; 95% confidence interval, 0.18-0.99; P = 0.03) by the Cox proportional hazard model but were unrelated to responses to the other three antigens. Patients with a preexisting response to any of the four antigens were significantly more likely to have a further vaccine-boosted response to that same antigen (P < 0.0001-0.036). CONCLUSIONS: There was a correlation between vaccine-induced CD8+ T-cell responses to melanoma-associated antigens and improved clinical outcome, but the correlation depended on the antigen against which the response is directed. The only significant correlation was with responses to MAGE-3.
Subject(s)
Antigens, Neoplasm/immunology , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Lymphocyte Activation , Melanoma/immunology , Melanoma/therapy , Neoplasm Proteins/immunology , Adult , Aged , Disease-Free Survival , Female , Histocompatibility Testing , Humans , Male , Melanoma/pathology , Melanoma/surgery , Middle Aged , Multivariate Analysis , Neoplasm Staging , Proportional Hazards ModelsABSTRACT
Profusamente ilustrado con fotografías, este texto es una exposición completa y actual, sobre neoplasias de la piel. Obra exelente. Su índice es: biología de la invasión y metástasis cancerosas cutáneas, epidemiología, posibles precursores de procesos malignos apidérmicos, carcinoma de células basales,escamosas y carcinoma verrugoso, oncogénesis viral en malignidades cutáneas, papulosis bowenoide, epidermodisplasia verruciforme, detección temprana de melanomas malignos: papel del exámen médico y el autoexámen de la piel, nevos displásicos, lesiones precursoras: nevos melanocíticos congénitos, melanoma maligno: correlaciones clinicopatológicas y tratamiento, factores pronóstico que influyen en la supervivencia de personas con melanoma maligno cutáneo, carcinomas de los anexos de la piel, enfermedad de Paget mamaria y extramamaria, lesiones seudosarcomatosas (neoplásicas y no neoplásicas) de la piel y tejidos superficiales, carcinoma de células de Merkel, neoplasias vasculares de la piel y asociadas con el SIDA, linfomas de células T cutáneos, enfermedades genéticas que predisponen a procesos malignos, cánceres metastáticos en la piel, manifestaciones dermatológicas de procesos malignos internos, nevo de grandes células fusiformes o epitelioides(nevo de Spitz), queratoacantoma, seudolinfomas cutáneos, técnicas de biopsia y principios quirúrgicos generales en el tratamiento del cáncer de piel, curetaje y electrodesecación terapéuticos, criocirugía, quimioterapia, cirugía con láser, cirugía plástica reconstructiva, radioterapia, inmunoterapia en el tratamiento de melanomas malignos, comprensión y tratamiento psicológico del paciente, el papel del oftalmólogo, problemas medicolegales en el manejo con pacientes con cáncer cutáneo
Subject(s)
Humans , Skin Neoplasms , Skin Manifestations , Mohs Surgery/methods , Mohs Surgery , Mohs Surgery/instrumentation , Cryosurgery/adverse effects , Cryosurgery/instrumentation , Cryosurgery/methods , Mechlorethamine/therapeutic use , Surgery, Plastic/methods , Surgery, Plastic/standards , Biopsy/instrumentation , Biopsy/methods , Biopsy/standards , Melanoma/classification , Melanoma/physiopathology , Melanoma/therapy , Fluorouracil/therapeutic use , Lasers/therapeutic use , Immunotherapy/methods , Radiotherapy/adverse effects , Radiotherapy/methods , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/pathologyABSTRACT
Profusamente ilustrado con fotografías, este texto es una exposición completa y actual, sobre neoplasias de la piel. Obra exelente. Su índice es: biología de la invasión y metástasis cancerosas cutáneas, epidemiología, posibles precursores de procesos malignos apidérmicos, carcinoma de células basales,escamosas y carcinoma verrugoso, oncogénesis viral en malignidades cutáneas, papulosis bowenoide, epidermodisplasia verruciforme, detección temprana de melanomas malignos: papel del exámen médico y el autoexámen de la piel, nevos displásicos, lesiones precursoras: nevos melanocíticos congénitos, melanoma maligno: correlaciones clinicopatológicas y tratamiento, factores pronóstico que influyen en la supervivencia de personas con melanoma maligno cutáneo, carcinomas de los anexos de la piel, enfermedad de Paget mamaria y extramamaria, lesiones seudosarcomatosas (neoplásicas y no neoplásicas) de la piel y tejidos superficiales, carcinoma de células de Merkel, neoplasias vasculares de la piel y asociadas con el SIDA, linfomas de células T cutáneos, enfermedades genéticas que predisponen a procesos malignos, cánceres metastáticos en la piel, manifestaciones dermatológicas de procesos malignos internos, nevo de grandes células fusiformes o epitelioides(nevo de Spitz), queratoacantoma, seudolinfomas cutáneos, técnicas de biopsia y principios quirúrgicos generales en el tratamiento del cáncer de piel, curetaje y electrodesecación terapéuticos, criocirugía, quimioterapia, cirugía con láser, cirugía plástica reconstructiva, radioterapia, inmunoterapia en el tratamiento de melanomas malignos, comprensión y tratamiento psicológico del paciente, el papel del oftalmólogo, problemas medicolegales en el manejo con pacientes con cáncer cutáneo
